Chromatin insulators and nuclear BTB/POZ proteins

The BTB/POZ is an evolutionarily conserved protein/protein interaction motif. It is present both in cytoplasmic proteins believed to contribute to the organization of the cytoskeleton, and in nuclear proteins, several of them appearing involved in human cancerogenesis. Nuclear BTB/POZ proteins usually interact (directly or indirectly) with DNA and are therefore presumably devoted to the regulation of genetic expression. Recent studies in Drosophila demonstrate that some of the DNA cis-acting sequences bound by nuclear BTB/POZ proteins (encoded br the mod(mdg4) and trithorax-like genes) are insulator elements which are unable to directly modulate promoter activity but can shield them from the influence of both enhancer and silencer elements. Both genetical and biochemical evidences point to the role of nuclear BTB/POZ proteins, in particular those encoded by mod(mdg4) and trithorax-like, in the regulation of chromatin modeling. Moreover, most of them form large homomultimeric complexes in vitro and/or in vivo so that they are able to bring together distant cis-regulatory elements when bound to DNA. These properties can, in part, underly the ability of some of them to directly regulate insulator activity.